Since the 1960s of the last century, many countries have been researching chemical ingredients of ginkgo leaves by adopting a modern separation technology, and it is found that biological activities of multiple aspects of ginkgo leaves are related to the specific chemical ingredients contained in ginkgo leaves through pharmacologic experiments and clinical verifications. Dr. Willar Schwabe of Germany registered a simple extract of the ginkgo leaves for the first time, and applied for patents (W Schwabe DE176708 and DE2117429) in 1972, named EGb761, for treating cardiovascular and cerebrovascular diseases and nervous system diseases, with a remarkable therapeutic effect and without toxic side effects. Ginkgolids have a platelet-activating factor (PAF) antagonism. Ginkgo preparations are listed as therapeutic medications in Germany, France and China, other countries list Ginkgo preparations as health care foods or over-the-counter medications, and Ginkgo health care foods developed in the United States of America have been approved by FDA.
Ginkgolids belong to terpenoids, referred to as terpene lactones, consist of sesquiterpene lactone and diterpene lactone, and are one kind of important active ingredient in the ginkgo leaves. Bilobalide belongs to sesquiterpene lactone, was obtained through separation by R. T. Major in 1967 and K. Weinges in 1969, and is the only sesquiterpene lactone compound found in ginkgo leaves so far. Ginkgolids A, B, C, M and J are diterpene lactone compounds, were separated from ginkgo leaves by S. Furukawa in 1932 for the first time, and were further separated and the chemical structures thereof determined by K. Nakanish, M. Maruyama and K. Okabe in 1967. From a structural point of view, the molecular skeleton of bilobalides consists of 15 carbon atoms, has 4 five-membered rings, i.e. one five-membered carbon ring and three five-membered lactone rings, which are mutually condensed, wherein one tertiary butyl rare in a natural product is connected to the five-membered rings. The bilobalide is very strong in biological activity, has a function of promoting nerve growth, may prevent function change caused by oxidative stress of brain cell mitochondria, improve the memory function of old people, prevent senile dementia, and prevent brain and spinal cord nerve demyelination, and has stronger neurotrophy and neuroprotection than those of ginkgolides. Ginkgolide B has functions of resisting inflammation and shock, protecting heart and cerebral vessels, treating acute pancreatitis and the like. However, the molecular skeleton of ginkgolides consists of 20 carbon atoms, has 6 five-membered rings, i.e. 2 five-membered carbon rings, 3 five-membered lactone rings and 1 tetrahydrofuran ring, the two five-membered carbon rings are connected together in a volute form, and the left rings are connected in a condensing form to form a special rigid cage-shaped three-dimensional chemical structure. Ginkgolide molecules have tertiary butyls rare in a natural product. Ginkgolides comprise diterpene lactones and sesquiterpene lactones, the diterpene lactones mainly include ginkgolides A, B, C, J and M, and the sesquiterpene lactones include bilobalide.
After PAF was found in the early 70s of the 20th century, pharmacologists researched bilobalide, and confirmed that ginkgo terpene lactone is a platelet-activating factor antagonist and has a function of protecting the immune system, central nervous system and ischemia injury and a function of resisting shock, irritability and inflammation. Ginkgolides A, B, C, M and J are structurally different in the number of hydroxyls and positions of connecting the hydroxyls. Ginkgolides all are the platelet-activating factor antagonist, and a key ingredient of special physiological activity in ginkgo leaves.

Structural formula of ginkgolide A, molecular formula: C20H24O9, molecular weight: 408.4

Structural formula of ginkgolide B, molecular formula: C20H24O10, molecular weight: 424.4

Structural formula of ginkgolide C, molecular formula: C20H24O11, molecular weight: 440.4

Structural formula of bilobalide, molecular formula: C15H18O8, molecular weight: 326.3
Ginkgolides have a strong specificity inhibition function to a platelet-activating factor PAF receptor, wherein the PAF-resisting activity of ginkgolides is highest. The PAF is one kind of endogenous phospholipid generated by secretion of platelets and multiple kinds of inflamed tissues, is a most-effective platelet aggregation inducer found so far, and is closely related to generation and development of many diseases.
However, ginkgolides are regarded as a natural PAF receptor antagonist with the highest clinical application prospect, and its antagonistic activities are closely related to chemical structures. When R3 in a lactone structure is a hydroxyl or the number of hydroxyls is increased, the antagonistic activity to the PAF is weakened; and when R2 is a hydroxyl and R3 is H, the antagonistic activity is remarkably improved, wherein the antagonism of ginkgolide B to the PAF is strongest.
There are many methods for extracting and purifying ginkgolides, mainly including a solvent extraction method, a column extraction method, a solvent extraction-column extraction method, a supercritical extraction method and a chromatographic or column chromatographic purification method. These methods may not effectively separate high-content ginkgolides, and each composition proportion of ginkgolides is uncertain, therefore, pharmacological functions on the clinical use are different; and because ginkgolides are low in contents, and have certain safety risks, and no complete pharmacologic and toxicologic and clinical test data, the above methods all are in a testing stage and are not implemented in a pharmaceutical production process. Although there are relevant patents of ginkgolide injections in China, their compositions are different from those of the present invention; and through searching in multiple official websites in ICH member countries, no other ginkgolide injection products are available on the market so far. At present, ginkgolide ingredients are determined by mostly adopting an HPLC to UV method, an HPLC-MS method and an HPLC-ELSD method. These methods only determine the contents of each ingredient of ginkgolides, but do not actually reflect the quality characteristics of the drugs due to the absence of strict control on adverse reactive materials in the products, and thus fail to form a perfect drug quality control system. Although there are many patents for invention directed to ginkgolides, because the control methods are too simple and the composition proportions of the ginkgolides are uncertain, no traditional Chinese medicine injection can be made, and no clinical effect and application safety can be ensured.
Although there are many patents and reports about ginkgolides in China, Germany and other countries, the technological process, the quality control technology and the clinical applicability of the present invention are entirely different from those of other patents for invention, especially, the ingredients of terpene lactones obtained by different separation and purification processes are different. So far, no process reports of extracting a combination of effective parts of ginkgolides with a fixed proportion of four components (ginkgolides A, B and C and bilobalide) are available, nor are reports of fingerprint control technologies of four components in the ginkgolides and inspection methods of possibly remained macromolecules and proteins. The ginkgolide injection prepared by the present invention has obtained an approval number from the State Food and Drug Administration, with GYZZ of Z20110035, and is a first injection of effective parts of ginkgo in the world, and is distinct and clear in structure.